Background and Objectives: The long-term effects of 棺-radiation on angiographically normal reference segments have not been defined well. This study was performed to evaluate the long-term morphological changes of reference segments after irradiation with a 188rhenium (Re)-filled balloon catheter system. Subjects and Methods: From 1999 to 2001, 41 patients received brachytherapy for de novo lesions with a 188Re-filled balloon catheter at least 10 mm longer than the length of an implanted stent. Among them, 25 patients had follow-up (f/u) angiogram at least 18 months after radiation therapy and 16 of them also had 6 month f/u angiogram. There were no differences in baseline clinical and angiographic parameters between the patients who received long-term f/u angiogram and those who did not. IVUS images at the same site were acquired at 3 different sites of the nonstented adjacent segment at 2, 4, and 5 mm from the stent margin and mean of these values were used for the analysis. Results: Post-radiation and long-term f/u IVUS images of 5 mm segments from the stent margin were available in 19 irradiated patients (RG: 36 segments) and theses were compared with those of 15 (28 segments) control patients (CG). There were no differences in baseline clinical and angiographic characteristics between the 2 groups. Mean angiographic f/u time was 26짹9 and 27짹8 mo for CG and RG respectively. No significant differences in post-intervention IVUS variables (external elastic membrane (EEM), lumen area, plaque and media (P&M) areas) were found between the 2 groups. In f/u IVUS, EEM (14.7짹4.5 vs. 12.1짹3.0mm², p=0.02) and P&M areas (7.8짹2.6 vs. 6.1짹2.6mm², p=0.02) were significantly larger in RG than in CG. Serial morphological analysis in RG showed that EEM and P&M area were significantly increased during 6 month after brachytherapy. However, no significant morphological changes were occurred after 6 month. Conclusion: Positive remodeling and plaque growth occurred in non-stented adjacent segments after brachytherapy. Most of these changes were occurred during 6 mo after brachytherapy and maintained at least for 2 years without significant luminal narrowing.